Grapevine leafroll-associated virus 3: a global threat to grapevine and wine industries but a gold mine for scientific discovery

Grapevine leafroll disease is the most damaging viral disease afflicting global grape and wine production. Of the five viruses likely to be associated with the disease, grapevine leafroll-associated virus 3 (GLRaV3) is believed to be the predominant agent, albeit its role as the causal agent has remained uncertain. GLRaV3 (species Ampelovirus trivitis, genus Ampelovirus, family Closteroviridae) has the third largest single-stranded, positive-sense RNA genome among plant viruses at ~18.5 kb, only surpassed by two other members of the family Closteroviridae, citrus tristeza virus and GLRaV1. GLRaV3 is unique among plant viruses in several ways, including the size of its genome, the long non-coding regions, and its association with the outer mitochondrial membrane for viral replication. Unfortunately, our understanding of the molecular mechanisms governing GLRaV3 genome replication, gene expression, and virus-host interactions is poor due to many factors. These include the unavailability of infectious cDNA clones and, until recently, an effective experimental system to initiate grapevine infection with viral clones. In this review, we capture recent advances in GLRaV3 research towards the establishment of infectious clones, grapevine inoculation systems, as well as approaches to elucidating the function of GLRaV3-encoded proteins. We also present a working model to explain GLRaV3 pathogenesis.